ID   NOVH_STRNV              Reviewed;         600 AA.
AC   Q9L9G0;
DT   16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT   11-JUL-2012, sequence version 2.
DT   03-AUG-2022, entry version 91.
DE   RecName: Full=Novobiocin biosynthesis protein H;
DE            EC=6.-.-.-;
GN   Name=novH;
OS   Streptomyces niveus (Streptomyces spheroides).
OC   Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC   Streptomyces.
OX   NCBI_TaxID=193462;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 23965 / DSM 40292 / JCM 4252 / NBRC 12917 / NCIMB 11891 / NRRL
RC   2449;
RX   PubMed=10770754; DOI=10.1128/aac.44.5.1214-1222.2000;
RA   Steffensky M., Muhlenweg A., Wang Z.X., Li S.M., Heide L.;
RT   "Identification of the novobiocin biosynthetic gene cluster of Streptomyces
RT   spheroides NCIB 11891.";
RL   Antimicrob. Agents Chemother. 44:1214-1222(2000).
RN   [2]
RP   FUNCTION, PATHWAY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC   STRAIN=ATCC 23965 / DSM 40292 / JCM 4252 / NBRC 12917 / NCIMB 11891 / NRRL
RC   2449;
RX   PubMed=11325587; DOI=10.1016/s1074-5521(01)00009-6;
RA   Chen H., Walsh C.T.;
RT   "Coumarin formation in novobiocin biosynthesis: beta-hydroxylation of the
RT   aminoacyl enzyme tyrosyl-S-NovH by a cytochrome P450 NovI.";
RL   Chem. Biol. 8:301-312(2001).
CC   -!- FUNCTION: Together with NovI, involved in the formation of a beta-OH-
CC       Tyr intermediate in the novobiocin biosynthesis pathway, an
CC       aminocoumarin family antibiotic that targets bacterial DNA gyrases. The
CC       ATP-dependent AMP-binding region activates L-Tyr as L-tyrosyl-AMP and
CC       then transfers the L-tyrosyl group to the acyl carrier domain through
CC       thioester formation to form a tyrosyl-S intermediate that is covalently
CC       tethered to NovH (L-Tyr-S-NovH). {ECO:0000269|PubMed:11325587}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=1.39 mM for L-Tyr {ECO:0000269|PubMed:11325587};
CC         KM=0.84 mM for p-Br-DL-Phe {ECO:0000269|PubMed:11325587};
CC         KM=0.89 mM for L-Phe {ECO:0000269|PubMed:11325587};
CC         KM=2.17 mM for 3-Cl-L-Tyr {ECO:0000269|PubMed:11325587};
CC         KM=6.13 mM for 3-Me-L-Tyr {ECO:0000269|PubMed:11325587};
CC         Note=kcat is 15 min(-1) with L-Tyr as substrate. kcat is 0.44 min(-1)
CC         with p-Br-DL-Phe as substrate. kcat is 0.13 min(-1) with L-Phe as
CC         substrate. kcat is 0.23 min(-1) with 3-Cl-L-Tyr as substrate. kcat is
CC         0.0083 min(-1) with 3-Me-L-Tyr as substrate.;
CC   -!- PATHWAY: Antibiotic biosynthesis; novobiocin biosynthesis.
CC       {ECO:0000269|PubMed:11325587}.
CC   -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC       {ECO:0000305}.
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DR   EMBL; AF170880; AAF67501.2; -; Genomic_DNA.
DR   AlphaFoldDB; Q9L9G0; -.
DR   SMR; Q9L9G0; -.
DR   KEGG; ag:AAF67501; -.
DR   BioCyc; MetaCyc:MON-18084; -.
DR   UniPathway; UPA01035; -.
DR   GO; GO:0016874; F:ligase activity; IDA:UniProtKB.
DR   GO; GO:0043642; P:novobiocin biosynthetic process; IDA:UniProtKB.
DR   Gene3D; 1.10.1200.10; -; 1.
DR   Gene3D; 3.30.300.30; -; 1.
DR   Gene3D; 3.40.50.12780; -; 1.
DR   InterPro; IPR010071; AA_adenyl_domain.
DR   InterPro; IPR036736; ACP-like_sf.
DR   InterPro; IPR025110; AMP-bd_C.
DR   InterPro; IPR045851; AMP-bd_C_sf.
DR   InterPro; IPR020459; AMP-binding.
DR   InterPro; IPR020845; AMP-binding_CS.
DR   InterPro; IPR000873; AMP-dep_Synth/Lig.
DR   InterPro; IPR042099; ANL_N_sf.
DR   InterPro; IPR009081; PP-bd_ACP.
DR   InterPro; IPR006162; Ppantetheine_attach_site.
DR   Pfam; PF00501; AMP-binding; 1.
DR   Pfam; PF13193; AMP-binding_C; 1.
DR   Pfam; PF00550; PP-binding; 1.
DR   PRINTS; PR00154; AMPBINDING.
DR   SUPFAM; SSF47336; SSF47336; 1.
DR   TIGRFAMs; TIGR01733; AA-adenyl-dom; 1.
DR   PROSITE; PS00455; AMP_BINDING; 1.
DR   PROSITE; PS50075; CARRIER; 1.
DR   PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE   1: Evidence at protein level;
KW   Antibiotic biosynthesis; Ligase; Phosphopantetheine; Phosphoprotein.
FT   CHAIN           1..600
FT                   /note="Novobiocin biosynthesis protein H"
FT                   /id="PRO_0000423997"
FT   DOMAIN          526..600
FT                   /note="Carrier"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   REGION          505..526
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         561
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ   SEQUENCE   600 AA;  63315 MW;  195E16673ECBF319 CRC64;
     MFNTRANKAS DQSPTIPTES ATLAELWERT VRSRPSSPAI VTNGETLSYD EVNARANRLA
     RLLLDEGAGP GRLVALALPR SSHLVISVLA VAKAGAVFLP LDVNHPRERL SYQLADARPA
     LLCTVRSAAA RLPDGIEMPR VLLDSPERTA VLDALPDTDL TDDERGGPLA ATDLAYVIYT
     SGSTGRPKGV ALTGAGLPAL AAAKVAAMRV TGDSRVLQFA SPGFDAYLTE LLAAFTAGAT
     LVVPGTDTLA GDPLRRALRD GRVSHAVLPP AAVATMSPDA VPDLRVLVVA GEACPAGLVE
     RWAPGRLLIN AYGPTECTVC ATMTGPLTPT DEVTIGRPIP GVSVYILDAE RRPAAPGEIG
     ELYLSGAGLA QGYLNSPDLT AQMFVPNPFA ADGERMYRTG DLASRRADGD ILFHGRIDDQ
     VELRGFRVEL GEVESVLSQH PDVAQAVAAL WTDPAEGPQL VTYVVPAPGT TPSAGELREH
     AGRFLPDFMV PSAFTTIDAV PLTPGGKTDR AGLPDPVKAT QPAGLGPRTP AEKVLCDIFR
     DLFDLVEIDV RSNFFEMGGN SILAVDLIQR AQEAGLTLMP RTVIDHPTIE QLAAIATLEE